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2.
Clin Lymphoma Myeloma ; 9(1): 110-2, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19362990

ABSTRACT

Recent data on the close association between chronic cold agglutinin disease (CAD) and Waldenström's macroglobulinemia (WM) have provided a new potential for therapeutic achievements. In 90% of patients with CAD, the cold agglutinins are monoclonal immunoglobulin Mkappa antibodies and clonal lymphocytes can be detected by flow cytometry of bone marrow aspirates. Bone marrow lymphoplasmacytic lymphoma is found by histology and immune histochemistry in 50% of the patients. Thus, CAD represents a spectrum of clonal lymphoproliferative disorders overlapping with WM. Conventional therapies are ineffective. Two prospective trials and 1 population-based retrospective study have shown partial response to rituximab monotherapy in 50%-55%, using strict response criteria. Median response duration was 11 months. We are currently running a prospective, uncontrolled trial of rituximab and fludarabine combination therapy. Although the preliminary results are encouraging, superiority over rituximab monotherapy remains to be proven. Patients with CAD requiring therapy should be included in clinical trials.


Subject(s)
Anemia, Hemolytic, Autoimmune/immunology , Waldenstrom Macroglobulinemia/immunology , Anemia, Hemolytic, Autoimmune/drug therapy , Cryoglobulins/biosynthesis , Humans , Waldenstrom Macroglobulinemia/blood , Waldenstrom Macroglobulinemia/therapy
3.
Rheumatology (Oxford) ; 46(4): 572-8, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17317717

ABSTRACT

Hepatitis C virus (HCV) infection is the major cause of mixed cryoglobulinaemia (MC), an immune complex (IC)-mediated systemic vasculitis mainly involving the small blood vessels. The precise mechanism of cryoprotein production is currently unknown. HCV virions and non-enveloped core protein participate in the formation of cold-insoluble ICs. Cryoglobulinaemic patients represent a distinct HCV-infected population, in that significant HCV enrichment of lymphoid cells is accompanied by evidence of productive virus infection and increased frequency of B cells. Liver, the major target organ of HCV, is the site of accumulation of inflammatory infiltrates that shares many architectural features with lymphoid tissue and reflects a distorted homeostatic balance between factors that enhance cellular recruitment, proliferation and retention, and those that decrease cellularity (cell death and emigration). There is now overwhelming evidence of a direct contribution to B-cell growth and survival through production of a variety of cytokines and chemokines. Liver tissue over-expression and abnormal circulating levels of B-cell activating factor belonging to the TNF family can provide effective costimulatory mechanisms to sustain the B-cell clonal expansion, which constitutes molecular stigmata of MC. Indolent lymphoproliferation might act as the starting point of chronic, multistage lymphomagenesis. An innovative therapeutic strategy is directed to 'eradication of the virus' and deletion of B-cell clonalities.


Subject(s)
Cryoglobulinemia/virology , Hepatitis C, Chronic/complications , B-Lymphocytes/pathology , Cell Proliferation , Cryoglobulinemia/therapy , Cryoglobulins/biosynthesis , Humans , Lymphoid Tissue/virology , Lymphoma, B-Cell/virology , Vasculitis/virology
4.
Eur J Immunol ; 33(4): 1020-9, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12672068

ABSTRACT

MRL.Fas(lpr/lpr) mice, a model for systemic lupus erythematosus (SLE) and arthritis in humans, have a Fas mutation that results in spontaneous development of systemic autoimmune diseases and a short life span. Half of them die by 5-6 months of age due to massive progression of systemic autoimmune diseases, such as lupus nephritis. However, C57BL/6 (B6).Fas(lpr/lpr) strain does not develop such disorders within the normal life span, indicating that suppressor gene(s) in B6 mice may control the onset and exacerbation of disease. Here, we show that the gene for a unique inhibitory Fc receptor for IgG (Fc gamma RIIB) is a critical SLE suppressor. Fc gamma RIIB-deficient B6.Fas(lpr/lpr) (B6.IIB(-/-)Fas(lpr/lpr)) mice developed systemic autoimmune diseases, including anti-DNA and anti-type II collagen autoantibodies and cryoglobulin production, immune complex glomerulonephritis and arthritis. They were short-lived, due to enhanced autoantibody production by B cells culminating in fatal lupus nephritis. Thus, Fc gamma RIIB deletion with Fas mutation is sufficient for the development of systemic autoimmunity in B6 mice. The inhibitory signaling cascade via Fc gamma RIIB may be critical for suppressing SLE in humans.


Subject(s)
Antigens, CD/physiology , Autoimmune Diseases/immunology , Receptors, IgG/physiology , fas Receptor/genetics , Animals , Antigens, CD/genetics , Arthritis/immunology , Autoantibodies/biosynthesis , Autoimmune Diseases/genetics , Autoimmune Diseases/pathology , B-Lymphocytes/immunology , Cryoglobulins/biosynthesis , Glomerulonephritis/immunology , Immunization, Passive , Immunoglobulin G/administration & dosage , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Mice , Mice, Inbred C57BL , Mice, Inbred MRL lpr , Mice, Knockout , Mutation , Receptors, IgG/genetics
5.
Clin Exp Immunol ; 123(1): 88-93, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11168003

ABSTRACT

Monoclonal IgM in type II mixed cryoglobulins (MC) preferentially use 51p1-related immunoglobulin VH genes. In normal preimmune B lymphocytes, 51p1-related gene expression is proportional to the germ-line gene dosage, which can be 0-4. To determine whether 51p1-related gene dosage influences the occurrence of type II MC or the VH gene bias in cryoglobulin IgM, we studied 47 patients chronically infected with hepatitis C virus (HCV), 24 MC+, 23 MC-. By Western analysis, 11 cryoprecipitate IgM (46%) were detected by G6 (a marker for 51p1-related gene products), eight (33%) by Staphylococcal Protein A (a VH3 family marker), and five (21%) by neither, indicating a 23-fold bias favouring 51p1-related genes. All 11 MC+, G6+ patients possessed > or = 1 copy of a 51p1-related gene; nine of the 36 others had none. The mean copy number of 51p1-related genes was greater in MC+ than MC- patients, and in MC+, G6+ patients versus the 36 others (P < 0.04), but significant differences were not seen in analyses restricted to patients with > or = 1 copy of a 51p1-related gene. We conclude that when a 51p1-related gene is present, a strong bias favours G6+ IgM in HCV-associated type II MC, but this bias is not greatly increased by a high dosage of 51p1-related genes. Furthermore, patients lacking 51p1-related genes also produce MC, but with G6- IgM.


Subject(s)
Cryoglobulins/biosynthesis , Gene Dosage , Genes, Immunoglobulin , Hepatitis C, Chronic/immunology , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Cryoglobulins/analysis , Cryoglobulins/genetics , Female , Genetic Markers/immunology , Genotype , Hepatitis C, Chronic/genetics , Humans , Immunoglobulin Heavy Chains/biosynthesis , Immunoglobulin M/analysis , Immunoglobulin M/biosynthesis , Immunoglobulin M/genetics , Immunoglobulin Variable Region/biosynthesis , Male , Middle Aged , Phenotype
6.
Pediatr Dermatol ; 17(2): 97-9, 2000.
Article in English | MEDLINE | ID: mdl-10792795

ABSTRACT

Childhood pernio is an uncommon condition described mainly through isolated case reports. We examined the cutaneous spectrum, clinical associations, presence of cryoproteins, and evolution of the condition in children, and performed a retrospective case series evaluation of children with pernio seen at a single ambulatory care university center over a 10-year period. Cases were drawn from a population of 3.2 million. Follow-up was at least 3 years. We found four boys and four girls with pernio. Distribution of skin lesions was on the fingers, toes, and ears. Four children had cryoglobulins or cold agglutinins, two had a positive rheumatoid factor, and none had a positive ANA or ANA profile. All eight cleared within 3 months and did not recur over at least a 3-year period. We concluded that childhood pernio is uncommon and may be associated with the presence of cryoproteins.


Subject(s)
Chilblains/diagnosis , Cryoglobulins/analysis , Adolescent , Biopsy, Needle , Chilblains/physiopathology , Child , Child, Preschool , Colorado , Cryoglobulins/biosynthesis , Female , Humans , Male , Prognosis , Retrospective Studies
8.
Int Immunol ; 5(5): 525-32, 1993 May.
Article in English | MEDLINE | ID: mdl-8318455

ABSTRACT

The autosomal recessive mutant gene, lpr, has been shown to accelerate the progression of lupus-like autoimmune disease, which is associated with a massive expansion of a unique CD4-CD8- double-negative T cell subset, in MRL/MpJ mice. Here we report a substrain of MRL/MpJ-lpr/lpr (MRL-lpr) mice which live almost twice as long with delayed development of glomerulonephritis, compared with conventional MRL-lpr mice. This substrain, termed MRL-lpr.II (II for long-lived), develops generalized lymphadenopathy characteristically seen in MRL-lpr mice. However, the expansion of a double negative lpr T cell subset is markedly limited with a mean value of 15% in their lymph nodes compared to about 70% in conventional MRL-lpr mice. Overall production of autoantibodies, such as anti-DNA and rheumatoid factors, does not significantly differ between the two MRL-lpr mice. However, serum levels of cryoglobulins, whose major component is IgG3, are markedly diminished in MRL-lpr.II mice with a parallel decrease in IgG3. Since MRL-lpr.II mice still carry the lpr mutation, as documented by the presence of defects in the Fas antigen, a possible new mutation in this substrain may play a significant role in the pathogenesis of lupus-like autoimmune syndrome.


Subject(s)
Autoimmune Diseases/genetics , Mice, Mutant Strains/genetics , Mice, Mutant Strains/immunology , T-Lymphocyte Subsets/immunology , Animals , Autoantibodies/biosynthesis , Cryoglobulins/biosynthesis , Female , Genes, Recessive , Glomerulonephritis/genetics , Glomerulonephritis/immunology , Glomerulonephritis/pathology , In Vitro Techniques , Longevity/genetics , Lymphocyte Activation , Male , Mice , Species Specificity , Syndrome
9.
Proc Natl Acad Sci U S A ; 90(6): 2345-9, 1993 Mar 15.
Article in English | MEDLINE | ID: mdl-8460145

ABSTRACT

An IgG3 monoclonal antibody, 6-19, derived from unmanipulated MRL/MpJ-lpr/lpr mice, exhibiting cryoglobulin and anti-IgG2a rheumatoid factor activities, induces skin leukocytoclastic vasculitis and glomerulonephritis when injected into normal mice. To determine the role of the gamma 3 heavy chain constant region in the generation of cryoglobulins and associated tissue lesions, we have established an IgG1 class switch variant, clone SS2F8, from the 6-19 hybridoma by sequential sublining. Here we report that the SS2F8 monoclonal antibody, which loses the cryoglobulin activity but retains the rheumatoid factor activity, fails to generate skin and glomerular lesions. The lack of pathogenicity of the IgG1 SS2F8 switch variant is not due to mutations in variable regions, since nucleotide sequence analysis shows no differences between both clones. In addition, we have observed that the IgG1 SS2F8 switch variant exhibits < 10% of the rheumatoid factor activity, as compared with the IgG3 6-19 monoclonal antibody, suggesting that the self-associating property of the gamma 3 isotype promotes antibody-binding activity. The present study indicates that the cryoglobulin activity associated with the gamma 3 isotype is critically involved in the pathogenicity of 6-19 anti-IgG2a rheumatoid factor monoclonal antibody and highlights the pathogenic relevance of autoantibodies of the IgG3 subclass in murine systemic lupus erythematosus.


Subject(s)
Antibodies, Monoclonal/immunology , Glomerulonephritis/immunology , Immunoglobulin Constant Regions/immunology , Immunoglobulin G/immunology , Immunoglobulin Heavy Chains/immunology , Rheumatoid Factor/immunology , Skin/immunology , Vasculitis, Leukocytoclastic, Cutaneous/immunology , Animals , Antibodies, Monoclonal/toxicity , Base Sequence , Cloning, Molecular , Crosses, Genetic , Cryoglobulins/biosynthesis , Enzyme-Linked Immunosorbent Assay , Female , Glomerulonephritis/pathology , Immunoglobulin Constant Regions/toxicity , Immunoglobulin Fab Fragments/immunology , Immunoglobulin Fab Fragments/toxicity , Immunoglobulin G/classification , Immunoglobulin G/toxicity , Immunoglobulin Heavy Chains/toxicity , Kidney/immunology , Kidney/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred Strains , Molecular Sequence Data , Oligodeoxyribonucleotides , Polymerase Chain Reaction , Skin/pathology , Vasculitis, Leukocytoclastic, Cutaneous/pathology
11.
Eur J Immunol ; 19(11): 2131-7, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2599002

ABSTRACT

The Yaa gene (Y chromosome-linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive lpr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus-like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and lpr genes in the development of the autoimmune syndrome, the Y chromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus-like nephritis in MRL mice was investigated in comparison with those bearing the lpr mutation. The Yaa gene as well as the lpr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus-like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the lpr gene (50% mortality rate: 7 months). This may be related to the finding that the lpr gene enhanced the production of a large spectrum of autoantibodies, including anti-DNA, rheumatoid factors and anti-gp70, and of cryoglobulins, whereas only anti-gp70 production among the autoantibodies studies was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW X MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice.


Subject(s)
Lupus Erythematosus, Systemic/genetics , Mice, Mutant Strains/immunology , Animals , Antibodies, Antinuclear/biosynthesis , Antigen-Antibody Complex/metabolism , Autoantibodies/biosynthesis , Complement C1q/immunology , Cryoglobulins/biosynthesis , Glomerulonephritis/genetics , Glomerulonephritis/immunology , Glomerulonephritis/pathology , Lupus Erythematosus, Systemic/immunology , Mice , Mice, Mutant Strains/genetics , Rheumatoid Factor/biosynthesis , Y Chromosome
12.
J Immunol ; 143(2): 526-32, 1989 Jul 15.
Article in English | MEDLINE | ID: mdl-2738401

ABSTRACT

A total of 20 of 23 IgG3 mAb derived from unmanipulated autoimmune MRL/MpJ-lpr/lpr mice was shown to generate cryoglobulins which were composed exclusively of IgG3. Although three IgG3 mAb failed to develop cryoglobulins, they were able to bind nonspecifically to any IgG3 molecules as efficiently as cryoprecipitable IgG did. The direct role of the gamma 3 constant region for the generation of cryoglobulins was demonstrated by the following findings: 1) the cryoglobulin activity was independent of the specificity of the IgG3 mAb, 2) no mAb other than those of the IgG3 subclass, including IgM rheumatoid factors (RF), generated cryoglobulins, and 3) the cryoglobulin activity was gained after the Ig class switch of mAb from IgM to IgG3. Analysis of Ig components in three different sources of cryoglobulins, either induced by the injection of bacterial LPS or by the infection with Plasmodium yoelii in BALB/c mice or developed spontaneously in MRL/MpJ-lpr/lpr mice, revealed the selective concentration of IgG3 in these cryoglobulins; greater than 99%, 73% and 58% of IgG recoverable from these three cryoglobulins, respectively, were IgG3. This further attests to the major role of IgG3 in the generation of cryoglobulins in mice. In addition, the enhanced formation and even induction of IgG3 cryoglobulins in the presence of IgM anti-IgG3 RF mAb, and the enrichment of IgM RF in LPS- or malaria-induced cryoglobulins indicated that IgM RF can be involved in the generation of cryoglobulins by interacting with noncryoprecipitable IgG3 as well as cryoprecipitable IgG3.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Cryoglobulins/biosynthesis , Immunoglobulin G/administration & dosage , Animals , Antibody Specificity , Cryoglobulins/immunology , Female , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Lipopolysaccharides/administration & dosage , Malaria/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Precipitin Tests , Rheumatoid Factor/administration & dosage , Rheumatoid Factor/metabolism , Species Specificity
13.
Eur J Immunol ; 19(2): 273-8, 1989 Feb.
Article in English | MEDLINE | ID: mdl-2495223

ABSTRACT

Previously we have demonstrated that eight out of nine IgG3 monoclonal antibodies (mAb) obtained from autoimmune MRL-lpr/lpr mice were able to self-associate and to precipitate in the cold (Gyotoku et al., J. Immunol. 1987. 138:3785). To determine whether the cryoprecipitation of IgG3 mAb is enhanced or inhibited in the presence of specific ligand, we have established eight IgG3 mAb reactive with 2,4-dinitrophenol (DNP) hapten: four mAb were obtained from fusion of spleen cells of C57BL/6 mice immunized with 2,4,6-trinitrophenylated keyhole limpet hemocyanin, three from 129/Sv and one from BALB/c immunized with DNP-lipopolysaccharide. Five of them induced cryoglobulins composed exclusively of the IgG3 mAb. The binding of negatively charged monomeric DNP-amino acid conjugates completely inhibited the cryoprecipitation of all the five cryoprecipitating anti-DNP IgG3 mAb, while the incubation with positively charged or neutral DNP-amino acid conjugates had variable effects: increase, inhibition or no change of the cryoprecipitation. In addition, positively charged DNP-amino acid conjugates were able to induce the cryoprecipitation of one of the non-cryoprecipitating anti-DNP IgG3 mAb. Our data showed that (a) IgG3 mAb derived from non-autoimmune strains of mice, similar to IgG3 mAb derived from an autoimmune MRL-lpr/lpr strain, possessed the unique property to self-associate and were able to form cryoglobulins in most cases; (b) although the Fc-Fc interactions of IgG3 mAb play a decisive role in IgG3 cold solubility, IgG3 cryoprecipitation was markedly influenced after interacting with their specific ligand, depending on the charge of the hapten-amino acid conjugate. This suggested that even minor interferences with the electrostatic equilibrium of the IgG3 by the binding of charged hapten molecules induced dramatic changes in the solubility of the IgG3 mAb at low temperature.


Subject(s)
Amino Acids/immunology , Antibodies, Monoclonal/immunology , Binding, Competitive , Dinitrobenzenes/immunology , Factor VIII/antagonists & inhibitors , Fibrinogen/antagonists & inhibitors , Immunoglobulin G/immunology , Nitrobenzenes/immunology , Animals , Anions , Antibodies, Monoclonal/physiology , Cryoglobulins/biosynthesis , Dinitrophenols/immunology , Factor VIII/biosynthesis , Fibrinogen/biosynthesis , Immunoglobulin G/physiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Myeloma Proteins/immunology , Oligopeptides/immunology
14.
Zentralbl Bakteriol Mikrobiol Hyg A ; 265(1-2): 45-56, 1987 Jun.
Article in English | MEDLINE | ID: mdl-3314259

ABSTRACT

The production of a protein insoluble at low temperature ("cryoprotein"), by cultures of Clostridium botulinum type G has been shown to be a metabolic characteristic also shared by C. botulinum type C and by C. subterminale. These new cryoproteins have been purified and some of their chemical and immunological properties studied. It was found that both proteins were chemically very similar among themselves and to the cryoprotein isolated from C. botulinum type G. All these proteins are formed by a single polypeptide chain of approximately Mr = 180,000, with closely related amino acid compositions, isoelectric points and do not contain either free cysteine or disulfide bridges. Homologous and heterologous radioimmunoassays established the existence of an antigenic similitude among the cryoproteins from C. botulinum type G and C. subterminale thus becoming the first purified antigens which relate both bacterial species. If the production of cryoproteins can be shown to be a generalized phenomenon within the genus Clostridium these substances would provide an important tool to examine immunological and genetical relatedness between strains in this bacterial group.


Subject(s)
Antigens, Bacterial/analysis , Bacterial Proteins , Clostridium botulinum/metabolism , Clostridium/metabolism , Cryoglobulins/biosynthesis , Amino Acids/analysis , Antigens, Bacterial/biosynthesis , Antigens, Bacterial/immunology , Chromatography, Gel , Clostridium/classification , Clostridium/immunology , Clostridium botulinum/classification , Clostridium botulinum/immunology , Cross Reactions , Cryoglobulins/immunology , Electrophoresis, Polyacrylamide Gel , Neutralization Tests , Radioimmunoassay , Solubility
16.
Haematologia (Budap) ; 14(3): 247-56, 1981.
Article in English | MEDLINE | ID: mdl-7035308

ABSTRACT

Immune hemolytic anemia can be treated by blood transfusion, steroids, cytotoxic drugs, plasmapheresis, and splenectomy. However, the benefits of therapy are dependent upon the relationship of treatment to the etiology of disease. Thus, effective therapy requires sufficient diagnostic precision to distinguish between allogeneic and autologous antibodies, recognize the etiologic role of immunogenic drugs, and define the immunoglobulin classes of both cold and warm reactive autoantibodies along with their complement interactions.


Subject(s)
Anemia, Hemolytic, Autoimmune/diagnosis , ABO Blood-Group System/immunology , Agglutinins , Anemia, Hemolytic/chemically induced , Anemia, Hemolytic, Autoimmune/drug therapy , Anemia, Hemolytic, Autoimmune/therapy , Autoantibodies/biosynthesis , Cryoglobulins/biosynthesis , Erythroblastosis, Fetal/etiology , Erythroblastosis, Fetal/immunology , Female , Hemoglobinuria, Paroxysmal/diagnosis , Hemoglobinuria, Paroxysmal/therapy , Humans , Immune Adherence Reaction , Immunoglobulin A/biosynthesis , Immunoglobulin M/biosynthesis , Infant, Newborn , Infectious Mononucleosis/immunology , Isoantibodies , Methyldopa/adverse effects , Paraproteinemias/diagnosis , Penicillins/adverse effects , Pregnancy , Temperature , Transfusion Reaction
18.
Lancet ; 1(8163): 285-7, 1980 Feb 09.
Article in English | MEDLINE | ID: mdl-6101740

ABSTRACT

Cryoimmunoglobulins seem to differ from non-cryoimmunoglobulins in not having carbohydrate groups, most probably sialic acid residues. It is proposed that cryoimmunoglobulinaemia is a physiological event and that desialylated immunoglobulins are a normal byproduct of the immune system. The rise in serum levels of cryoimmunoglobulins is either a pre-secretory event which follows enhanced stimulation of B lymphocytes or a post-secretory event secondary to the generation of serum neuraminidase-like activity by invading microorganisms or their products. It is also proposed that the liver is the main organ which removes cryoimmunoglobulins from the serum. The removal is mediated by specific hepatocellular receptors for desialylated glycoprotein. Clinical or subclinical liver diseases are therefore commonly associated with significantly increased levels of serum cryoglobulins.


Subject(s)
Cryoglobulins , Paraproteinemias/etiology , Chemical Phenomena , Chemistry , Cryoglobulins/biosynthesis , Cryoglobulins/immunology , Humans , Infections/immunology , Liver/metabolism , Paraproteinemias/immunology , Receptors, Fc/metabolism
19.
Arthritis Rheum ; 22(9): 983-7, 1979 Sep.
Article in English | MEDLINE | ID: mdl-383087

ABSTRACT

The distribution and amount of fibronectin in both involved and uninvolved skin from scleroderma patients and controls were compared by indirect immunofluorescence. A marked increase in fibronectin was found in the deep dermis of involved scleroderma skin, while the subepidermal papillary regions of all specimens revealed little variation in fibronectin content. The districution of the accumulated fibronectin appeared to parallel that of the accumulated collagen in the involved reticular dermis.


Subject(s)
Cryoglobulins/biosynthesis , Scleroderma, Systemic/pathology , Skin/metabolism , Adult , Collagen/biosynthesis , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged
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